Rosemary Cooke was the youngest of three children. But for the past decade, she has grown up as an only child. Her sister, Fern, disappeared when she was five; her brother, Lowell, left home more than 10 years ago to find her.

“The last time I saw him, I was 11 years old and he hated my guts,” Rosemary tells readers.

When it comes to Karen Joy Fowler's outstanding new novel, We Are All Completely Beside Ourselves, you want to be extremely careful to avoid spoilers. If someone tries to describe the plot to you, just stick your fingers in your ears and recite loudly: “La, la, la – I can't hear you.” Or quit reading this review now and go buy the book before some well-meaning individual wrecks it for you.

While Rosemary says that "some will have guessed," the twist at the heart of the novel, this reader sure didn't. The revelation was totally unexpected – and the consequences of what it meant unexpectedly powerful. To have it described in advance just makes the novel sound quirky, a disservice to writer and reader.

For readers who only know Fowler from 2004's charming and impeccably-timed bestseller, “The Jane Austen Book Club,” her new novel will land with the force of a haymaker. In a novel that blends fiction and science, Fowler takes on what it means to be a family, the nature of memory and grief, and where the dividing line between the human and humanity lies. Fowler is so good at character and sneaky profundity that it's easy to forgive a few muddled chapters' worth of plot near the end.

Rosemary – who used to be a happy chatterbox, overflowing with words – starts in the middle, as her professor father advised when he was too tired to listen to her prattle anymore.

The middle takes place in 1996, when she's a fifth-year college student at the University of California, Davis. Slowly, the details of a family decimated by grief start to emerge: Her dad is an alcoholic who enjoys fly-fishing on his front lawn, her mom has suffered at least one nervous breakdown, and her beloved older brother is wanted by the FBI. Of Fern, there is no word.

“The middle of my story is all about their absence, though if I hadn't told you that, you might not have known. By 1996, whole days went by in which I hardly thought of either one,” says Rosemary, although this turns out to be an act of will more than the merciful fading of the pain of a long-ago tragedy.

She and her parents deal with the gaping hole at the center of their family by resolutely not talking – not about her sister, brother, or anything controversial or potentially painful. “My parents persisted in pretending we were a close-knit family, a family who enjoyed a good heart-to-heart, a family who turned to each other in times of trial. In light of my two missing siblings, this was an astonishing triumph of wishful thinking; I could almost admire it.”

For her part, she pretends that she's okay to protect her fragile mother, an act she's put on since she was bullied relentlessly during middle school. “The only thing I could do for her now was to be okay. I worked at that as if it were my job. No complaints to management about worker conditions.”

Two events occur that force Rosemary to confront what happened to her family: Her mother gives her her old journals (which an airline promptly loses), and Lowell knocks on her door. Rosemary actually chose her college in hopes that he might find her: The FBI said his last known sighting was near UC-Davis.

Rosemary stands “for remembrance,” a mentally unstable, Shakespeare-loving theater student tells her. But she was five when Fern disappeared and, as she tries to piece together what happened, she's having trouble telling her actual memories from what she's been told occurred.

“Before, many things that happened are missing from my memory or else stripped down, condensed to their essentials like fairy tales,” says Rosemary. “Once upon a time, there was a family with two daughters, and a mother and father who'd promised to love them both exactly the same.”

As a furious pre-teen, Lowell blamed Rosemary for what happened to his favorite sister. The now grown-up girl is afraid that if she confronts the past, she'll find that he was right. (At least partly to protect herself from guilt, she is self-righteously, habitually furious with her pedantic father.) But while Rosemary has been afraid to let herself long for – or even think about – her siblings for years, she's been shaped by her relationship to them, nonetheless. And when she does break her long silence about what happened to Fern, the events are devastating enough to remake the life of every member of her family.

“My brother and my sister have led extraordinary lives. I wasn't there, and I can't tell you that part. I've stuck here to the part I can tell, the part that's mine, and still everything I've said is all about them, a chalk outline around the space where they should have been," she says. "Three children, one story.”